Activation and polarization of microglia are involved in neuroinflammation and regulate ischemic stroke-associated brain injury. Protein arginine methyltransferase 8 functions as a regulatory component of hypoxic stress-induced neuroinflammation. The protective effect of protein arginine methyltransferase 8 (PRMT8) against ischemic strokeassociated brain injury through regulation of microglia activation and polarization was investigated. First, PRMT8 was downregulated in middle cerebral artery occlusion (MCAO)-induced mice and oxygen−glucose deprivation/reoxygenation (OGD/R)-induced SH-SY5Y. Injection with AAV-PRMT8 reduced infarct volumes in MCAO-induced mice. Moreover, injection with AAV-PRMT8 promoted neuronal survival and ameliorated histopathological changes in the brains of MCAO-induced mice. The neuronal apoptosis and neuroinflammation in MCAO-induced mice were suppressed by AAV-PRMT8 injection. Second, PRMT8 overexpression increased cell viability and suppressed the cell apoptosis and inflammation of OGD/R-induced SH-SY5Y. Third, injection with AAV-PRMT8 reduced almost 50% of CD86 + M1 microglia and enhanced about 20% of CD206 + M2 microglia. Furthermore, PRMT8 overexpression attenuated OGD/R-induced M1 phenotype polarization of BV2. Lastly, PRMT8 upregulated Lin28a and loss of Lin28a attenuated PRMT8 overexpression-induced increase in cell viability and decrease in cell apoptosis and inflammation of OGD/R-induced SH-SY5Y. In conclusion, PRMT8 promoted M2 phenotype polarization of microglia and suppressed neuronal apoptosis to ameliorate cerebral ischemia/reperfusion injury through upregulation of Lin28a.
Background Symptomatic intracranial haemorrhage (SICH) is a severe and deadly complication in patients with large vessel occlusion (LVO) who receive endovascular treatment (EVT). Recent studies have indicated that many risk factors, including pretreatment scores and the operation process, may be associated with the occurrence of SICH after thrombectomy. This study aims to identify independent risk factors and establish a novel nomogram-based model for patients with anterior LVO to predict the occurrence of SICH after direct thrombectomy or bridge therapy (thrombectomy based on intravenous thrombolysis). Methods Patients with acute ischaemic stroke after EVT to recanalize the blocked artery in anterior circulation were consecutively recruited from November 2017 to March 2019. Baseline information was collected from each patient. These data were subsequently analysed by R Project for Statistical Computing. Results A total of 127 patients with complete data were classified into the training set, among whom 37 patients (29.1%) fulfilled the criteria for SICH. The results of the multivariate analyses showed that NIHSS (P=0.024), ASPECT (P<0.001) and ASITN (P=0.017) scores were independently associated with the occurrence of SICH after thrombectomy. Ultimately, three independent pretreatment predictors were included in the NIHSS/ASPECT/ASITN (NAA) prediction model, and the receiver operating characteristic analysis results showed an area under the curve (AUC) of 0.845 (95% CI=0.763–0.928). The calibration plots showed that the actual observations were consistent with the measured and predicted results of the nomogram. Conclusions In this study, a novel model based on NAA for predicting the occurrence of SICH after thrombectomy in patients with anterior LVO was established and validated internally. The results suggest that this model can help improve perioperative evaluations and individualized treatment strategies.
In the present study, fluorophenyl retinoic acid triazole, a retinoic acid derivative having more bioavailability compared to the parent retinoic acid was investigated against cell growth and proliferation. The results indicated that fluorophenyl retinoic acid triazole leads to a significant expression of TRK mRNA in time a dependent manner in NB1643 cells. There were about 10-, 14-, and 21-fold induction of expression after 1, 2, and 3 days of treatment, respectively. The results revealed that TRK and TRKB were induced at 6 and 12 hours afterthe treatment respectively and the expression of TRKB was maximum at day 3. Fluorophenyl retinoic acid triazole exerts neurite outgrowth activity by inducing TRKB expression, which is a receptor for brain -derived neurotrophic factor and a protein-tyrosine kinase. Fluorophenyl retinoic acid triazole accumulation generates many small vesiclesin the cell which assembles at the neck of each small prominence and lead to significant morphological changes after 24 hours of treatment.
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